7. Project Summary/Abstract The prevalence of food allergies has increased dramatically in the United States and around the world. Given the rate at which allergic disease has increased, multiple environmental factors, including changes to our diet, are likely culprits. For example, increased consumption of fruits and vegetables and adherence to a Mediterranean diet decreases the risk of allergic disease while diets high in fat and fast foods increase this risk. However, the role of non-nutritive components, such as bitter tasting phytochemicals, in the development or prevention of food allergies is not known. Bitter tasting phytochemicals were once ubiquitous in our diets but modern agriculture and food science techniques have all but eliminated them from most of our food supply. Therefore, it is paramount that we understand how their absence in our modern diet shapes the intestinal immune system and affects the development of food allergies. This project will investigate how sensory epithelial cells in the gastrointestinal tract sense bitter tastants and how they integrate this information with other sensory modalities to evaluate the overall quality of the ingested food. Specifically, we will use an in vitro model system to study enteroendocrine cell responses to varying ratios of bitter tastants to macronutrients. Complementary to these studies, we propose to use single cell RNA sequencing to measure rare epithelial cell types? responses to bitter tastants in vivo. We will also study how bitter tastant sensing in the gut shapes the composition of the immune system and how this affects the development of allergic disease. Specifically, we will use a combination of flow cytometry, qPCR, and in vitro models to investigate dendritic cells, T cells, and B cells in the small intestine and their activation, migration, and effector functions in response to bitter tastant sensing at steady state and in the context of allergic inflammation. The potential impact of this research will be the development of dietary guidelines and medical interventions that take into account the non-nutritive components of our food such as phytochemicals and bitter tastants.